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Molecular and Cellular Biochemistry

, Volume 461, Issue 1–2, pp 47–56 | Cite as

Downregulation of long non-coding RNA TUG1 suppresses tumor growth by promoting ubiquitination of MET in diffuse large B-cell lymphoma

  • Hai Cheng
  • Zhiling Yan
  • Xue Wang
  • Jiang Cao
  • Wei Chen
  • Kunming Qi
  • Dian Zhou
  • Jieyun Xia
  • Na Qi
  • Zhenyu Li
  • Kailin XuEmail author
Article

Abstract

Long non-coding RNAs (lncRNAs) can modulate gene expression through different mechanisms, but the fundamental molecular mechanism between lncRNAs and MET protein in diffuse large B-cell lymphoma (DLBCL) was poorly understood. The expression of lncRNA TUG1 and MET in DLBCL tissues and cell lines was determined by quantitative real-time PCR and western blotting. Cell proliferation, invasion and apoptosis were determined by cell counting kit-8 assay, transwell assay and flow cytometer. The animal xenograft model was established by the injection of DLBCL cells carrying si-TUG1. The expression of TUG1 and MET was upregulated in DLBCL tissues and cells. We demonstrated that MET was altered in the TUG1 knockdown DLBCL cells, and confirmed the interaction between TUG1 and MET by RNA pull-down and RNA immunoprecipitation. Furthermore, knockdown of TUG1 reduced MET protein level by promoting ubiquitination, and suppressed tumor growth in vitro and in vivo. Our findings demonstrated that TUG1 exerted its oncogenic function in DLBCL by inhibiting the ubiquitination and the subsequent degradation of MET. Knockdown of TUG1 through MET downregulation suppressed DLBCL cell proliferation and tumor growth.

Keywords

Diffuse large B-cell lymphoma Invasion Long non-coding RNA MET TUG1 Ubiquitination 

Notes

Funding

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81871263, 81770223, 81500097, and 81500088).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Institute Research Medical Ethics Committee of The Affiliated Hospital of Xuzhou Medical University.

Informed consent

All the patients were participating in this study with written informed consent.

Research involving human and animal participants

All animal experiments were proved by the Institute Research Medical Ethics Committee of Xuzhou Medical University, and all animals-treatment operations were executed according to the Xuzhou Medical University Ethical Guidelines for Animal Experiment.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hai Cheng
    • 1
  • Zhiling Yan
    • 1
  • Xue Wang
    • 1
  • Jiang Cao
    • 1
  • Wei Chen
    • 1
  • Kunming Qi
    • 1
  • Dian Zhou
    • 1
  • Jieyun Xia
    • 1
  • Na Qi
    • 1
  • Zhenyu Li
    • 1
  • Kailin Xu
    • 1
    Email author
  1. 1.Blood Diseases Institute, Xuzhou Medical University, Department of Hematology, Key Laboratory of Bone Marrow Stem CellThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina

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